Drug abuse and drug dependence is the second most common mental health disorder among young women in American today. Recent survey data also indicate that abuse of marihuana, cocaine, tobacco and alcohol by women is increasing. Yet the PHS Task Force on Women's Health Issues (1985) noted that there has been relatively little research on the health consequences of substance use and recommended "studies of the significant factors related to the onset, continuation and cessation of smoking, drinking and drug taking by women". The proposed clinical research center program focuses on the biological and behavioral antecedents, correlates and consequences of substance abuse by women. The safety and efficacy of new pharmacological treatments for cocaine, opiate and polydrug abuse will be evaluated in controlled inpatient and outpatient drug treatment programs. Parallel studies to determine if new pharmacotherapies effectively suppress cocaine self- administration in a female monkey drug self-administration model are proposed. Established operant behavioral procedures will be used to evaluate the dose range of pharmacotherapeutic efficacy and safety. Controlled clinical research ward studies are proposed to examine polydrug use patterns involving marihuana, alcohol and tobacco. Covariance between premenstrual dysphoria and drug use patterns will be examined. Neurobehavioral correlates of the development of tolerance to marihuana during chronic marihuana smoking will also be studied. Neurophysiologic and behavioral correlates of interactions between cocaine, marihuana and alcohol will be examined. Family history of substance abuse has been shown to be a significant factor in risk for polydrug abuse problems. The possible contribution of this antecedent risk factor to marihuana abuse will be evaluated by comparing sensitivity to the physiologic and behavioral effects of marihuana in women with and without a positive family history of alcohol abuse. Implementation of more effective drug abuse treatment programs and improved strategies for drug abuse prevention requires intensive analysis of biologic, behavioral and social concomitants of gender-related and gender specific factors in substance abuse.